Warning Letter: Beijing Taiyang Pharmaceutical Industry Co Ltd
The U.S. Food and Drug Administration (FDA) arrived at the drug manufacturing facility, Beijing Taiyang Pharmaceutical Industry Co., Ltd., located at No. 1 Shuang Qiao East Road, Chaoyang District, Beijing, on November 16, 2015, to conduct an inspection.
USFDA’s investigators documented that the firm limited and/or refused an FDA inspection. Under the Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Food and Drug Administration Safety and Innovation Act (FDASIA), section 707, 21 U.S.C. 351(j), the drugs are adulterated in that they have been manufactured, processed, packed, or held in an establishment where the owner or operator has limited inspection and refused inspection.
USFDA’s investigators also documented that the methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to current good manufacturing practice (CGMP). Accordingly, the drugs are adulterated within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).
USFDA reviewed the firm’s December 9, 2015, response in detail.
This letter summarizes the limitation of an inspection and significant deviations from CGMP for active pharmaceutical ingredients (API). USFDA’s investigators observed specific deviations including, but not limited to, the following.
1. The firm delayed, denied, or limited an inspection, or refused to permit the FDA inspection.
On November 16, 2015, USFDA’s investigators observed through a window a warehouse containing numerous drums bearing the company’s label. When USFDA’s investigators requested access to this warehouse, you barred them from entering the warehouse to examine the containers or the material in them without giving a reasonable explanation.
The following day, you gave USFDA’s investigators access to the warehouse. However, upon entry they observed that a significant number of drums had been removed and were not available for inspection. When they asked about the drums they had observed the previous day, you provided no explanation of the whereabouts or contents of the drums.
You delayed FDA’s access to the warehouse and limited FDA’s inspection by removing the drums before USFDA’s investigators could inspect them.
2. Failure to maintain complete data derived from all laboratory tests conducted to ensure compliance with established specifications and standards.
USFDA’s investigators observed systemic data manipulation across the facility. They documented unexplained deletions of laboratory test results. They discovered that you repeated tests until you obtained acceptable results and that you failed to investigate out-of-specification or otherwise undesirable test results. The firm relied on these falsified and manipulated test results to support batch release and stability data. The firm routinely re-tested high performance liquid chromatography (HPLC) samples and deleted previous chromatograms without justification. The management acknowledged that employees in the quality control laboratory have access, authority, and the ability to delete and repeat HPLC injections when undesirable results were encountered prior to reporting final results.
The response states repeated testing was due to quality control operators continuously injecting solvents until a stable baseline was achieved. The response also states the results of repeated tests were deleted to decrease the number of saved chromatograms on the hard drives. Any data created as part of a CGMP record must be evaluated by the quality unit as part of release criteria and maintained for CGMP purposes. In order to exclude data from the release criteria decision-making process, you must have valid, documented, scientific justification for its exclusion.
Reducing the number of records